Following his graduation from Princeton, Freneau tried his hand at teaching, but quickly gave it up. He also pursued a further study of theology, but gave this up as well after about two years. As the Revolutionary War approached in 1775, Freneau wrote a number of anti-British pieces. However, by 1776, Freneau left America for the West Indies, where he would spend time writing about the beauty of nature. In 1778, Freneau returned to America, and rejoined the patriotic cause. Freneau eventually became a crew member on a revolutionary privateer, and was captured in this capacity. He was held on a British prison ship for about six weeks. This unpleasant experience, detailed in his work, "The British Prison Ship" would precipitate many more patriotic and anti-British writings throughout the revolution and after.

In 1790 Freneau married, and became an assistant editor of the New York Daily Advertiser. Soon after, Madison and Thomas Jefferson worked to get Freneau to move to Philadelphia in order to edit a partisan newspaper that would counter the Federalist newspaper The Gazette of the United States. Jefferson, then head of the State Department, offered Freneau a position in Philadelphia as a State Department translator. Freneau accepted this undemanding position, which allowed him enough free time to head up the Democratic-Republican newspaper Jefferson and Madison envisioned.

This partisan newspaper, The National Gazette, provided a vehicle for Jefferson, Madison, and others to promote criticism of the rival Federalists. The Gazette took particular aim at the policies promoted by Alexander Hamilton, and like other papers of the day, would not hesitate to shade into personal attacks. Owing to The Gazette's frequent attacks on his administration, President George Washington took a particular dislike to Freneau.